Purchase this article with an account.
P.I. Murray, K.M. Wloka, V. Savant, C.M. Cheung, J.M. Faint, N. Amft, G.R. Wallace, C.D. Buckley, M. Salmon, S.J. Curnow; Topical Glucocorticoid Therapy Induces CXCR4 Up-Regulation on Primed Ocular Lymphocytes in Uveitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):678.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: It is now clear that certain constitutive chemokines have a pathological role in inflammation during disease, including CXCL12 (SDF-1) and its receptor CXCR4. We studied control of the CXCL12-CXCR4 axis during active intra-ocular inflammation. Methods: Aqueous humour (AqH) was obtained from 11 patients with active uveitis, and 12 patients undergoing surgery for age-related cataract. CXCR4 expression was examined on AqH and peripheral blood lymphocytes, as well as CD4+ T lymphocytes cultured in vitro with AqH. Levels of CXCL12, TGFß1 and TGFß2 were measured using multiplex bead immunoassays. Results: CXCR4 is normally only expressed at high levels by naïve CD45RA+ T lymphocytes. However, we found high levels of CXCR4 on primed CD45RO+ lymphocytes (CD4+ and CD8+) in uveitis AqH, especially in those patients receiving topical glucocorticoid (GC) at the time the sample was taken. The elevated expression of CXCR4 could be reproduced by in vitro culture of CD4+ T lymphocytes in AqH, with the highest levels induced by AqH from the GC-treated group, suggesting that the elevated expression in vivo was a result of the ocular microenvironment and not preferential recruitment of CXCR4hi cells from peripheral blood. GCs were able to directly increase expression of CXCR4 and migration in response to CXCL12. The glucocorticoid receptor antagonist mifepristone reduced the ability of GC-treated uveitis AqH to up-regulate CXCR4 expression, indicating that GC may be responsible for the high induction of CXCR4 in treated patients. In contrast, the lower levels of CXCR4 induced by non-inflammatory and untreated uveitis AqH were found to be dependent upon the presence of TGFß2. CXCL12 (SDF-1) was present in non-inflammatory AqH but was reduced to undetectable levels in uveitis AqH. Conclusions: The very high levels of CXCR4 induced by GC treatment, in the absence of significant CXCL12 in the inflamed eye, may result in the attraction of cells away from the eye leading to the resolution of inflammation observed following treatment.
This PDF is available to Subscribers Only